This is a continuous effort of a collaborative multi-phase project to investigate the immune response in both humans and experimental animals after their infection with human hepatitis C virus. In the initial phase, the commercial testing kits were used to detect antibodies to HCV proteins in the known non-A, non-B hepatitis patient sera. This provided information on the serological data of hepatitis C virus infection and its relationship to other clinical determinations. The second phase of the study will concentrate on the identification of immune dominant epitopes and neutralizing epitopes. The scope of this phase of study will be extensive and time-consuming. The third phase of the project will encompass using the knowledge of the immune response to develop preventive strategy and understanding of the pathogenicity of this viral infection. Special attention will be paid in identifying the possible relationship between the immune response and the high chronicity in HCV infected patients. One part of this study is to transfer techniques and procedures developed in the laboratory studies to our clinical studies. We have developed a proliferation assay to measure the immune response in mice to recombinant HCV core proteins. We then adopted the experience learned in working with mice to develop procedures to differentiate chronic infected patients from the recovered ones. During FY '95 and FY '96, we initiated a new project to examine the potential for a nucleic acid vaccine for HCV. The knowledge, the techniques and the material developed in this nucleic acid vaccine study will also complement our continued effort in understanding the immune response in HCV infection. The long-term goal of both projects will lead to developing models of immune therapy of chronic viral infection of the liver.